The protective effects and mechanisms of modified Lvdou Gancao decoction on acute alcohol intoxication in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. MATERIALS AND METHODS: AAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. RESULTS: MLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1ß and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Taken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.

Determination of in vivo biological activities of Dodonaea viscosa flowers against CCL4 toxicity in albino mice with bioactive compound detection.

Dodonaea viscosa L.Jacq. is an evergreen shrub and native to Asia, Africa, and Australia. It has been used as traditional medicine in different countries. The foremost objective of the current study was to discover the protective potential of D. viscosa flowers Methanol (DVM) and Chloroform (DVC) extracts against CCL4 induced toxicity in mice. This study was intended to identify phytochemicals through HPLC, GCMS, and FT-IR, as well as in vitro antioxidant and in vitro anti-tuberculosis activity. Our comprehensive findings indicate that Dodonaea viscosa is valuable and widespread herbal medicine through therapeutic potentials for curing various ailments. Dodonaeaviscosa flowersare found to have a protective effect against oxidative stress produced by CCL4 in the liver, kidney, and spleen. The intake of DV extracts restored the level of hepatic enzymes (ALP, AST ALT, and Direct bilirubin), hematological parameters (RBCs, WBCs, and Platelets), total protein, and liver antioxidant enzymes (SOD, GPx, and CAT) after a decline in levels by CCL4. Histopathological results discovered the defensive effect of 300 mg/kg of DVM extract against CCL4 induced damage, thus having an improved protective effect compared to DVC and control. As a result of metabolite screening, the total flavonoids and total phenolics were present in abundance. A phytochemical investigation by HPLC identified gallic acid, epicatechin, cumeric acid, flavonoids, while GCMS estimated oleic acid (Octadecenoic acid) (C18H34O2), Stearic acid (C18H36O2), Ricinoleic acid (C18H34O3), and Cedrol (C15H26O). DVM extract exhibited resistance against in vitro Mycobacterium tuberculosis strains. So this study proposed that the protective effect of DV against oxidative damage induced in the liver, kidney, and spleen can be correlated to the antioxidant compounds.

HLA-B*35:01 and Green Tea-Induced Liver Injury.

BACKGROUND AND AIMS: Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury. APPROACH AND RESULTS: Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5). CONCLUSIONS: Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.

Predictive effects of a combined indicator in patients with hepatocellular carcinoma after thermal ablation.

AIM: This study aimed to investigate the predictive power of the combination of Systemic Immune-Inflammation Index (SII) and albumin-bilirubin (ALBI) grade in prognosis outcomes of early-stage hepatocellular carcinoma (HCC) after thermal ablation. MATERIALS AND METHODS: This retrospective study was reviewed and approved by our institutional review board, and written informed consent was obtained from each patient. According to the Milan criteria, a total of 405 treatment-naïve patients with clinicopathologically confirmed HCC were enrolled who subsequently underwent thermal ablation from 2011 to 2016. The outcomes of overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were statistically analyzed. RESULTS: The median follow-up time of this study was 45.1 months (range, 1.3-83.2 months). After thermal ablation in patients with SII-ALBI Grades 1, 2, and 3, the cumulative 5-year OS rates were 81.7%, 63.2%, and 26.9%; the 5-year CSS rates were 82.4%, 67.5%, and 26.9%; and the 5-year RFS rates were 49.3%, 44.6%, and 25.3%, respectively (all P < 0.001). On multivariate Cox regression analyses, SII-ALBI was independently associated with the three outcomes after adjustment for various confounders (all P < 0.05). In addition, SII-ALBI played a predictive role in OS, CSS, and RFS for patients with negative alpha-fetoprotein (AFP) (P < 0.05). Compared with SII and ALBI, the AUCs for the prediction of OS and CSS using SII-ALBI were superior to single indicator (bothP < 0.05). CONCLUSION: Elevated preablation SII-ALBI is associated with shorter OS, CSS, and RFS in patients with early-stage HCC. Our indicator showed the potential to be a supplement tool for patients with negative AFP during follow-up.

Nucleoside analogs assisted with Chinese compound prescription in treating hepatic fibrosis of chronic hepatitis B patients: A protocol of systematic review and meta-analysis.

BACKGROUND: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients. METHOD: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis. RESULT: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA. CONCLUSION: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy. PROSPERO REGISTRATION NUMBER: CRD42020156859.

Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera's prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. METHODS: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36). RESULTS: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were "not reached" (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = -0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. CONCLUSIONS: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.

Effect of curcumin analogue synthetic product from cullilawan oil for the liver damage treatment in male mice (Mus musculus L.).

The active component in cullilawan oil can be synthesized into curcumin analogue product, which has pharmacological activity. The synthesis process by using conventional and microwave methods can produce different isomer products. Different synthesis products and models of animal are used to provide different hepatoprotective effects. The aim of this study was to use the curcumin analogue synthetic products (AKS-k and AKS-m) from cullilawan oil in male mice (Mus musculus L.) liver damage treatment induced by carbon tetrachloride (CCl4). The in vivo method was employed using biochemical of blood and histopathological images of liver cells as indicators. The results showed that the curcumin analogue synthetic product using microwave methods had better pharmacological effects than the conventional method product in terms of the results of blood biochemical analysis and microscopic images of liver cells.

Hepatoprotective and antioxidant activity of Dicliptera bupleuroides Nees. extracts on paracetamol induced hepatotoxicity in rats.

Aim of this study to evaluate the safety profile, hepatoprotective and in-vivo antioxidant activities of Dicliptera bupleuroides Nees. Toxicity studies were conducted in human RBCs and DNA by using standard procedures. Acute hepatoprotective investigation was carried out in albino rats by treated with all six fractions of D. bupleuroides 350 mg/kg/day. ALT, AST, ALP and total bilirubin (TB) were performed. The n-hexane fraction (200 mg/kg/day) exhibited appropriate hepatoprotective activity hence subjected to chronic study (14 days). Paracetamol induced the hepatotoxicity (350mg/kg) and silymarin (50 mg/kg) was standard drug. Liver function tests, liver peroxidation tests and histopathological examination were performed at the end. Hexane fraction showed significant decrease in the level of ALT (88.1±7.8), AST (93.8±7.6), ALP (136.3±8.4) and TB (0.6±0.03) as compared to the standard drug (p>0.05). Rats treated with ethyl acetate fraction showed decrease in MDA (42.8±0.7) while GSH was found to be increased (107.7±1.8) against the toxic group (51.3±2.9), (73.6±4.0) respectively. All the drug extracts decreased the oxidative stress and protect the DNA from free hydroxyl radicals. DNA damage protection activity of these fractions is due to phytochemicals present in these fractions. These results indicate that the plant fractions possess significant hepatoprotective and antioxidant activities with no toxic effects.

Fructus Psoraleae-Induced Severe Liver Injury and Treatment With Two Artificial Liver Support Systems: A Case Series Study.

To describe the clinical features and outcomes of patients with suspected Fructus Psoraleae (FP)-induced severe liver injury who underwent treatment with two artificial liver support systems (ALSSs). The cases of 12 patients with severe liver injury by FP were enrolled. We evaluated the tolerability of, and changes in biochemical parameters after treatment with plasma exchange combined with hemofiltration and double plasma molecular absorption system, and 6-month follow-up information were collected. The median age of the 12 patients was 60 years and nine (75%) patients were females. All patients had jaundice as the initial symptom. Two ALSS types were used to treat the patients. The group that underwent plasma exchange combined with hemofiltration showed remarkable improvements in ALT, AST, total bilirubin (TB), GGT and international normalized ratio levels (AST, TB, international normalized ratio, P < 0.01; ALT, GGT, P < 0.05), and the levels of AST, ALP, TB, and total bile acid decreased significantly in the double plasma molecular absorption system group after treatment (TB, P < 0.01; AST, ALP, total bile acid P < 0.05). During 6 months of follow-up, two patients died, two became chronic, and eight recovered to normal. FP can cause clinically severe liver injury, characterized by gastrointestinal symptoms and jaundice, which can lead to death or become chronic. Both ALSSs were safe and well tolerated in drug-induced liver injury patients. After ALSS treatment, the levels of biochemical indicators of liver function improved significantly, indicating that ALSS might be beneficial for patients with severe drug-induced liver injury.

A novel treatment strategy using indocyanine green for transarterial chemoembolization in BCLC stage C hepatocellular carcinoma.

PURPOSE: The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression-free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. RESULTS: For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple-drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). CONCLUSIONS: The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients.

Additional compounds and the therapeutic potential of Cnidoscolus chayamansa (McVaugh) against hepatotoxicity induced by antitubercular drugs.

Previously non-isolated compounds (scopoletin and ß-D-Glucopyranoside, (1R)-O-isopropyl 6-O-(2,3,4-tri-O-acetyl-ß-D-xylopyranosyl)-2,3,4-triacetate) were isolated from an organic extract of the Cnidoscolus chayamansa stem. Also, lupeol acetate (main compound, 49.7 mg/g of dry extract) and scopoletin (0.19 mg/g of dry extract) were quantified by HPLC analysis from this organic extract. The protective activity of the C. chayamansa organic extract against hepatotoxicity induced by antitubercular drugs [Rifampicin (50 mg/kg), Isoniazid (50 mg/kg), and Pyrazinamide (100 mg/kg)] are reported. The extract was tested at 200 and 400 mg/kg in Balb/C mice during 85 days, using silymarin (2.5 mg/kg) as positive control. Liver damage was determined using biochemical parameters (AST, ALT, ALP, CHOL, HDL TG, Urea, and CREA), histological analysis, and evaluation of oxidative stress (SOD, CAT, Gpx, Lpx and POx). The extract at both doses favored body weight gain with respect to the anti-TB group; the dose of 200 mg/kg was better. Also, the extract at both doses decreased the values of transaminases (AST, ALT) enzymes (p < 0.05) vs. anti-TB group. In oxidative stress parameters, the SOD value was decreased, as were the levels of peroxidation of lipids and oxidative protein in the group with C. chayamansa extract at 200 and 400 mg/kg vs. the anti-TB group. Histological analyses from liver showed the absence of steatosis in the extract group at 400 mg/kg, and moderate steatosis in the silymarin and extract (at 200 mg/kg) groups with respect to anti-TB group, which demonstrated a steatosis. It should be noted that during the study period, none of the treated mice died. In conclusion, the CHCl3: MeOH extract of C. chayamansa has a hepatoprotective effect against hepatotoxicity induced by anti-TB drugs.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.

Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users.

Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function.

Hypoglycemic and antioxidant effects of oral administration of garlic extract in the livers of type 1 diabetic rats.

Background Liver dysfunction is a predominant complication of diabetes. Herbal remedies such as garlic are commonly used for reducing diabetic complications. In this study the effect of garlic extract on glucose level, liver enzymes activities in the serum and nitric oxide (NO) level, oxidative stress status, and histology in the liver tissues of streptozotocin-induced diabetes (type 1) was investigated. Methods Twenty-four adult male Wistar rats were randomized and divided into four groups: control rats, diabetic rats, diabetic rats treated with garlic, and garlic-treated normal rats. Glucose level and liver enzymes activities were determined by colorimetric assay in the serum. NO levels by Griess method, oxidative stress parameters including malondialdehyde (MDA), total oxidative status (TOS), and total antioxidant capacity (TAC) by spectrophotometric method, and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Results Glucose level, liver enzymes activities, MDA, TOS, and NO levels were increased and TAC level decreased significantly in diabetic rats in comparison with control rats (p<0.01); whereas, after oral administration of garlic, glucose level, liver enzymes activities, MDA, TOS, and NO levels were decreased and TAC level increased significantly near to the normal levels (p<0.05). Conclusion The results showed the hypoglycemic and antioxidant effects of garlic in the livers of type 1 diabetic rats.

Cord-derived mesenchymal stem cells therapy for liver cirrhosis in children with refractory Henoch-Schonlein purpura: A case report.

RATIONALE: To explore the curative effect of human umbilical cord-derived mesenchymal stem cell (ucMSC) therapy for patients with liver cirrhosis complicated with immune thrombocytopenia and refractory Henoch-Schonlein purpura (HSP). PATIENT CONCERNS: A 12-year-old boy presented to our hospital with an 11-month history of purpura on the skin of both lower limbs accompanied by thrombocytopenia. The patient had a history of repeated swelling and painful dorsum pedis, followed by skin redness. DIAGNOSIS: Bone marrow slides showed megakaryocyte maturation disorder. Based on the pathology and drug abuse history, he was diagnosed with nodular cirrhosis, secondary allergic purpura, and thrombocytopenia, etiologies related to his drugs and an immune dysfunction. INTERVENTIONS: ucMSC transplantation was performed, the liver damaging drugs were discontinued, and the appropriate liver immunosuppressive drugs were administered. ucMSCs were injected 8 times/wk in 2 months, with a median cell count of 5.65 × 10/L, ranging from 5.48 to 5.98 × 10/L. OUTCOMES: As the patient's skin rash resolved, his platelets gradually increased to >150 × 10/L and liver transaminase levels gradually decreased to a normal level. Ultrasonography of the abdomen indicated that the round nodules in the liver decreased in size and that the spleen thickness also decreased. LESSONS: This is a unique case of significant HSP with associated thrombocytopenia in a patient with liver cirrhosis. Long-term oral administration of excessive herbal medicine may cause liver damage. We believe that ucMSCs provide a novel approach for the treatment of liver cirrhosis.

Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review.

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb-drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.

Phoenix dactylifera protects against oxidative stress and hepatic injury induced by paracetamol intoxication in rats.

The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group. These PCM-induced effects were associated with oxidative stress as demonstrated by increased levels of malondialdehyde (MDA) and reduced levels of hepatic antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Pretreatment of PLME decreased ALT and AST by 78.2% and tissue MDA by 54.1%, and increased hepatic GPx (3.5 folds), CAT (7 folds) and SOD (2.5 folds) compared to PCM group. These PLME-mediated effects were comparable to NAC pretreatment. Histological analysis demonstrates that PLME conserved hepatic tissues against lesions such as inflammation, centrilobular necrosis, and hemorrhages induced by PCM. In contrast, PLAE-mediated effects were less effective in reducing levels of liver function enzymes, oxidative stress, and liver histopathological profiles, and restoring antioxidant defenses against PCM-induced intoxication. These findings indicate that PLME exerts protective effects against PCM-induced hepatotoxicity via scavenging free radicals and restoring hepatic antioxidant enzymes. Thus, PLME and its bioactive components could further be evaluated for their pharmacological properties against drug-induced deleterious effects.